Journal of Medical Mycology xxx (xxxx) xxx

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Journal of Medical Mycology

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General review

Estimates of serious fungal infection burden in Coˆte d’Ivoire and country health profile

a, a a a a a b

D. Koffi *, I.V. Bonouman , A.O. Toure , F. Kouadjo , M.R.E. N’Gou , K. Sylla , M. Dosso , c,1

D.W. Denning

a

Parasitology and mycology department, Institut Pasteur de Coˆte d’Ivoire, 01 PoBox 490 Abidjan 01, Coˆte d’Ivoire

b

Bacteriology and virology department, Institut Pasteur de Coˆte d’Ivoire, Abidjan, Coˆte d’Ivoire

c

Manchester Fungal Infection Group, faculty of medicine, biology and health, university of Manchester and Manchester academic health science centre,

Manchester, UK

A R T I C L E I N F O A B S T R A C T

Article history: Due to limited access to more powerful diagnostic tools, there are few data on the burden of fungal

Received 15 September 2020

infections in Coˆte d’Ivoire, despite a high HIV and TB burden and many cutaneous diseases. Here we

Received in revised form 12 November 2020

estimate the burden of serious fungal infections in this sub-Saharan country with a health profiling

Accepted 17 November 2020

description. National demographics were used and PubMed searches to retrieve all published articles on

Available online 21 November 2020

fungal infections in Coˆte d’Ivoire and other bordering countries in West Africa. When no data existed, risk

populations were used to estimate frequencies of fungal infections, using previously described

Keywords:

methodology by LIFE (www.LIFE-Worldwide.org). The population of Coˆte d’Ivoire is around 25 million;

Fungal disease

37% are children (14 years), and 9% are > 65 years. in children is common, measured at

Coˆte d’Ivoire

Cryptococcosis 13.9% in 2013. Considering the prevalence of HIV infection (2.6% of the population, a total of 500,000)

Burden disease and a hospital incidence of 12.7% of , it is estimated that 4590 patients per year develop

Histoplasmosis cryptococcosis. For , it is suggested that 2640 new cases occur each year with the

Candidiasis prevalence of 11% of newly diagnosed HIV adults, and 33% of children with HIV/AIDS. Disseminated

AIDS

is estimated a 1.4% of advanced HIV disease – 513 cases. An estimated 6568 news cases of

TB

chronic pulmonary (CPA) occur after pulmonary tuberculosis (a 5-year prevalence of

6568 cases [26/100,000]). Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with

fungal sensitisation (SAFS) were estimated in 104/100,000 and 151/100,000 respectively, in 1,152,178

adult asthmatics. Vulvovaginal (VVC) is common and recurrent VVC affects 6% of women in

their fertile years – 421,936 women. An unknown number develop candidaemia and invasive

aspergillosis. The annual incidence of fungal keratitis is estimated at 3350. No cases of ,

and are described, although some cases of mycetoma and

Conidiobolus infection have been reported. This study indicates that around to 7.25% (1.8 million) of the

population is affected by a serious fungal infection, predominently tinea capitis in children and rVVC in

women. These data should be used to inform epidemiological studies, diagnostic needs and therapeutic

strategies in Coˆte d’Ivoire.

C

2020 Elsevier Masson SAS. All rights reserved.

Introduction to species that belong to one of these four genera: Cryptococcus,

Candida, or Pneumocystis. Epidemiological data for

Invasive fungal disease has a high attributable mortality unless fungal infections are poor because many are misdiagnosed and

diagnosed and treated promptly and appropriately. Nearly statistics are extrapolated from few (mostly geographically

2 million people die from invasive fungal infections each year in localized) studies.

the world [1]. Over 90% of fungal infection-related deaths are due Coˆte d’Ivoire (or Ivory Coast) is located in West Africa south of

the Sahara between 10 degree North latitude, 4 and 8 degree West

2

longitude. It has an area of 322,462 km and is bounded to the west

* Corresponding author.

by Liberia and Guinea-Conakry, to the north by Mali and Burkina

E-mail address: davidkoffi[email protected] (D. Koffi).

1

In association with the LIFE program at www.LIFE-Worldwide.org. Faso, to the east by Ghana and to the south by the Gulf of Guinea. https://doi.org/10.1016/j.mycmed.2020.101086

C

1156-5233/ 2020 Elsevier Masson SAS. All rights reserved.

D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx

The population of Coˆte d’Ivoire is characterized by a growth rate papers. Cryptococcal meningitis (CM) was estimated in adults only

of 2.6% per year and by the high proportion of its youth (41.5%) (it rarely occurs in children) at a rate of 12.7% among adult HIV/

[2]. The health status of the population is marked by high maternal AIDS patients with CD4 less than 200/mL [19]. PCP frequency was

and infant-juvenile mortality, partly due to inadequate health estimated by assuming 11% of newly diagnosed HIV/AIDS adults

services. The epidemiological profile is dominated by a high (risk spread over 2 years) and 33% HIV/AIDS children at risk (25% of

prevalence of HIV among those over 15 years of age as well as a those not on antiretroviral therapy) [20,21]. Disseminated histo-

high incidence of malaria among children under 5 and tuberculosis plasmosis was estimated from an autopsy study published in 1994

in the population, respectively 2.6% [3], 189.9 per 1000 (Annual [22], and assumed to relate to all advanced HIV cases in the country

Report on the Health Situation 2018) and 85 per 100,000 (80,000) over a 2 year risk period.

inhabitants (Annual TB notification case 2018) [4]. The national Regarding invasive fungal infections associated with hospital

health priorities are these three diseases (HIV, TB and malaria) and care (notably candidiasis and aspergillosis), we considered

recently the novel coronavirus disease 2019 (COVID-19) absorbing hematology malignancies [23], lung cancer [18], chronic obstruc-

all the funds allocated to the health system and hiding the urgency tive pulmonary disease (COPD) [24], ICU and assumed peritonitis

of opportunistic infections such as severe fungal diseases (SFIs). surgical patients based on neighbouring country data [25]. No

One of the best documented examples of underfunding for transplantation procedures are currently done in Coˆte d’Ivoire. For

fungal diseases is cryptococcosis. This disease is currently chronic infections, mainly chronic pulmonary aspergillosis (CPA),

responsible for 15–20% of deaths in individuals with AIDS, and we used the annual incidence of TB to calculate a annual incidence,

yet in 2015 it received 1% of the funding allocated to tuberculosis as described previously [14–16]. This was then used to compute a

[5]. Remedying this situation requires more advocacies by the five-year prevalence assuming a 15% annual mortality or surgical

infectious disease community as well as more studies document- cure rate. We also assumed that 67% of all CPA cases had prior TB as

ing the local, national and global burden of fungal diseases and the underlying disease. Invasive aspergillosis (IA), CPA and allergic

their impact on human health. bronchopulmonary aspergillosis (ABPA) and severe asthma with

Several studies documenting fungal disease in Coˆte d’Ivoire are fungal sensitization (SAFS) were estimated in adults only. Adult

published. Oral Candida infections were reported in paediatrics and asthma data came from To et al. as part of the World Health Survey

adult patients [6]. Reports on Aspergillus [7,8] and Pneumocystis on asthma [17]. We assumed that 2.5% of adult asthmatics had

pneumonia (PCP) infections are limited to few cases [9,10]. Asthma ABPA [26] and 30% of the worst 10% of asthmatics had SAFS,

is the most common chronic respiratory disease with hospitalisa- supported by a recent review on asthma in Africa [27].

tion rate of 5% [11] and allergic rhinitis (which may be partly fungal Tinea capitis prevalence was estimated based on a local study in

in aetiology) was the most common allergic disease [12]. school children [28]. Fungal keratitis annual incidence was

Estimates of the impact of diseases on public health, generally extrapolated from East Africa [29].

referred to as burden of disease, are valuable inputs for public

health authorities, developing appropriate surveillance of fungal

diseases and setting policy priorities. Many estimates of the Results and discussion

burden of serious fungal diseases are now published for over

60 countries with populations > 1 million [13]. Disease burden Population profile

should be considered as the underlying basis for health care

prioritisation in Coˆte d’Ivoire. The total population of Coˆte d’Ivoire was 22,671,331 inhabi-

Here we report on the burden of fungal disease in Coˆte d’Ivoire tants according to the results of the General Population and

focusing in particular on prevalence data and the reliability of Housing Census (RGPH) of 2014. In 2018, it is estimated at

current estimates. These data will contribute to the global SFIs 25,195,140 inhabitants (the basis of our estimates). About 48.4%

estimation project and awareness campaign, help reframe health are females and 48% of population live below the poverty line.

policy by bringing a numerical estimate for expanded advocacy, Poverty is unequally distributed among the regions of Coˆte d’Ivoire.

increased research, and improved laboratory diagnostic capacity The level of poverty varies from 22.7% in urban areas to 71.7% in

for the fighting of fungal infection. rural areas [30]. Moreover, with the scarcity of public resources,

investments in basic social services (health, education, infrastruc-

ture, etc.) have fallen considerably, leading to a decrease in the

Methods supply of these services. In terms of health resources, Coˆte d’Ivoire

had 2023 primary health care institutions (PHCI), 82 general

The methodology adopted is that previously described [14– hospitals and 17 regional hospitals, i.e. one PHCI for 12,006

16]. Initially, we performed a PubMed search using the Medical inhabitants and one reference hospital for 173,490 inhabitants

Subject Headings terms. Keywords were combined using the [31].

Boolean operator AND and OR. Search details are: (‘‘mycoses’’

[MeSH Terms] or ‘‘mycoses’’ [all fields] or (‘‘fungal’’ [all fields] and Overall disease profile

‘‘infection’’ [all fields]) or ‘‘fungal infection’’ [all fields]) and (‘‘Coˆte

d’Ivoire’’ [MeSH terms] or (‘‘cote’’ [all fields] and ‘‘d’Ivoire’’ [All In 2016, the incidence of endemic diseases (malaria, acute

Fields]) or ‘‘Coˆte d’Ivoire’’ [all fields] or (‘‘ivory’’ [all fields] and respiratory diseases, HIV/AIDS, tuberculosis) has declined, with the

‘‘coast’’ [all fields]) or ‘‘ivory coast’’ [all fields]). exception of diarrhea and sexually transmitted infections, which

Demographic data were obtained from the ‘‘Institut National de are on the rise. The WHO estimated the number of malaria cases at

la Statistique-Coˆte d’Ivoire’’ based on the 2014 Housing and 7,890,000 (5,720,000–10,740,000) in 2016. Since 1995, a National

Population Census [2]. For many estimations, we used specific Tuberculosis Program has been established to organize the fight

populations at risk (HIV/AIDS patients [3], patients with pulmo- against TB on a national scale. The tuberculosis notification rate in

nary TB [PTB] [4], asthma [17], cancer [18], burn patients [4], and 2016 was 89 notifications per 100,000 inhabitants, compared to

patients receiving critical care) to derive national incidence or 98 per 100,000 inhabitants in 2015. Of 21,299 tuberculosis cases,

prevalence estimates of SFIs, using validated data from the country 4608 (21.6%) were found to be HIV-positive [31].

or others nearby, if available. The incidence of chronic superficial The total prevalence of HIV infection in 2018 was 2.6% [3]. At

mycoses as obtained from those reported in the PubMed-retrieved the level of care for HIV patients, 44% (1013 sites) of health

2

D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx

Table 1

public sector is 2.7 midwives per 3000 women of reproductive age

HealthTechnical plateform and equipment available in the country (RASS 2018).

(WRA). The WHO minimum standards for human resources in

Technical plateform and equipment 2017 2018 health (1 doctor per 10,000 inhabitants, 1 nurse per 5,000

inhabitants and 1 midwife for 3,000 WRA) were reached in

Public lab of medical biology 231 253

Operating theater 89 99 2018 [31].

Ambulance 536 629 Otherwise, the budget granted by the State of Coˆte d’Ivoire to

Blood transfusion centers 162 162

the Ministry of Health and Public Hygiene fell from USD

Radiology department 84 85

$665,138,840 in 2017 to $650,292,813 in 2018, a decrease of

$14.8 million (À2.22%). This budget represents 5.3% of the general

State budget in 2018. This is lower than the commitments made by

the State of Coˆte d’Ivoire at the Abuja (Nigeria) summit in

2001 which is to devote 15% of the general state health budget [31].

facilities offered antiretroviral (ARV) care and treatment services.

There were 252,125 patients on ARVs including 12,347 children Mycology diagnostics

(4.9%) and 239,778 adults.

With regard to cancer in Coˆte d’Ivoire, 15,000 new cases are Only few laboratories (5) are capable of doing diagnostic tests

expected each year. Among these cancers, it is estimated that for fungal infection with conventional methods (culture, direct

271 cases of lung cancer (5-year prevalence) are diagnosed each examination), antifungal susceptibility testing and/or innovative

year, or 1.09% of all cancers [18,32]. technical detection or for identification (PCR, MALDI-TOF). India

ink microscopy in cerebrospinal fluid is the principal means of

Healthcare facility profile and human resources making the diagnosis of cryptococcal meningitis. Recent years

have seen the introduction of cryptococcal, Histoplasma and

Coˆte d’Ivoire registered 6732 functioning hospital beds in Aspergillus antigen lateral flow assays, as well as Elisa based

2018. The estimated number of critical care beds in 2018 was 673 assays. Only the first is available in Coˆte d’Ivoire and is not

(assuming 10% of hospital beds are occupied by critically ill extensively used. An Aspergillus antibody point of care assay with

patients). Transplants programs (solid organ and hematopoietic excellent sensitivity and specificity [33] has also been launched in

stem cell) do not exist in Coˆte d’Ivoire and there is no nationwide the last 2 years and is not yet available. All of these tests are WHO

registry of surgeries undertaken. essential diagnostics.

In terms of the technical platform and existing health A solution of choice for the early diagnosis of PCP in health

equipment (shown in Table 1), there were a total number of facilities without fiberoptic bronchoscopy is the examination of

99 operating theaters, 253 public medical biology laboratories, expectorated sputum or induced by inhalation of a hypertonic

85 radiology units, 629 ambulances and 162 blood transfusion solute [34]. Detection of in sputum or

centers in public health establishments in 2018 compared to bronchoalveolar lavage fluid can be by direct microscopy using

2017. However, it should be noted that at the level of health Gomori Methenamine Silver (GMS) or calcofluor white stain,

districts: 8.1% register at least one non-functional medical device immunoflurescence or PCR. Pneumocystis PCR is the most sensitive

in their public biology laboratory, 18.6% do not have an operating technique, is now a WHO essential diagnostic and is the only

theater, 26.7% do not have any radiology service and 2.3% do not means of diagnosing pneumocystosis in children [35]. None these

have a blood transfusion center [4]. Only few (9) centres undertake techniques are currently used in Coˆte d’Ivoire.

bronchoscopy with 40% belong to the private sectors and almost all

are based in Abidjan. Incidence and prevalence of serious fungal infections

Also in 2018, the Ministry of Health and Hygiene recorded a

ratio of physicians providing healthcare in the public sector of About 7.25% (1,827,204) Ivorians were estimated to be affected

1.4 physicians per 10,000 inhabitants. The ratio of nurses to health by SFIs. Table 2 shows the estimated total burden of fungal

care providers in the public sector is 2.3 nurses per 5000 inhabi- infections, the number of infections classified according to the

tants and the ratio of midwives to health care providers in the main risk factors as well as the rate for 100,000 inhabitants.

Table 2

Estimated incidence and prevalence of most serious fungal diseases in Coˆte d’Ivoire.

Infection Number of infection per underlying disorder per year Total burden Rate/100K

None HIV/AIDS Respiratory Cancer ICU

Esophageal candidiasis – 4665 – – – 4665 19

Oral candidiasis – 17,280 – – – 17,280 69

Candida peritonitis – – – – 189 189 0.75

Candidaemia – – – 882 378 1260 5

Recurrent candida vaginitis (4Â/year) 421,936 – – – – 421,936 1675

ABPA – – 28,804 – – 28,804 114

SAFS – – 38,022 – – 38,022 151

CPA 6568 – – 6568 26

Invasive aspergillosis – 640 852 58 – 1550 6.15

Cryptococcal meningitis – 4590 – – – 4590 18.22

Pneumocystis pneumonia – 2640 – – – 2640 10.48

Histoplasmosis 513 – – 513 2.04

Tinea capitis 1,295,786 – – – – 1,295,786 5143

Fungal keratitis 3350 3350 13.3

Total burden estimated 1,721,072 30,328 74,246 940 567 1,827,204

ABPA: allergic bronchopulmonary aspergillosis; SAFS: severe asthma with fungal sensitisation; CPA: chronic pulmonary aspergillosis; ICU: intensive care unit.

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D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx

Candida infections to be high. We calculated that SAFS affects 38,022 Ivorian adults

annually. ABPA and SAFS are collectively known as ‘‘fungal

There are no studies published on candidaemia or invasive asthma’’ which is responsive to antifungal therapy, and over

candidiasis in Coˆte d’Ivoire, so we have estimated a general rate of 40,000 adults probably suffer from this, as there is probably some

5/100,000 or 1260 cases of candidaemia annually [36]. Burned duplication between ABPA and SAFS prevalence. The long-term

patients are more likely to develop candidemia and other fungal natural history of fungal allergy is not well documented. Some

systemic lesions, as are HIV-positive patients [37]. Candidemia people have allergic fungal infection that comes and goes in

occurs in 2.5 to 7% of patients in intensive care units for burns severity, usually for unclear reasons. Mucus production and

[38]. In Coˆte d’Ivoire, the Abidjan center for burn victims receives mucosal swelling in the airways, nose and sinuses is the hallmark

about 500 burn patients a year. So nearly 25 will develop of fungal allergy.

candidemia [39]. We have assumed that 30% of candidaemia CPA is particularly common after pulmonary TB, and we

cases occur in intensive care. estimate and annual incidence of 1567 cases. However as this is a

For surgical ICU patients Candida peritonitis may develop in chronic condition, the overall prevalence will be higher, an

association with recurrent gastrointestinal perforations or anasto- estimated 6,568, of which 75% of cases are TB related and the

motic leakage after surgical intervention. Candida species are remainder to other pulmonary conditions such as sarcoidosis and

isolated between 70–90% of all patients with peritonitis [40]. Acute previous pneumothorax. Some patients have no underlying

peritonitis is a very common pathology. It occupies third place in condition at all, are usually misdiagnosed and TB. The key test

acute surgical abdomens after appendicitis and intestinal occlu- Aspergillus IgG antibody (or precipitins) is not available in Coˆte

sions. Its frequency is estimated, compared to all acute surgical d’Ivoire.

abdomens, to be 3% in France [41] and 20% in Mali [25]. If as in PCP exists in Coˆte d’Ivoire as evidenced by the autopsy study of

France we assume that the number of patients with intra- Coulibaly et al. who found in post-mortem a prevalence of 8.6% in

abdominal candidiasis is 50% of those with candidaemia [42], 70 HIV-infected patients [22]. This disease is caused by the

we estimate 189 such cases, but this may be a substantial opportunistic P. jirovecii, which is a life-threatening

underestimate. infection in HIV/AIDS patients. Compared with adults, HIV-positive

Esophageal candidasis occur frequently in HIV-infected children had a high prevalence of P. jirovecii pneumonia and a low

patients. We estimate 4665 cases based on 20% of new HIV- prevalence of tuberculosis. Almost a third of HIV-positive children

infected patients and 0.5% of those on ARVs [43]. HIV/AIDS adds had PCP, according to Lucas et al. [10], a rate similar to that found in

nearly 2 million cases of oral thrush and > 500,000 cases of affected children in industralized countries but much higher than

oesophageal fungal infections annually in the world [44]. Oral the incidence in adults in Abidjan. We can estimate 2640 cases of

fungal infections are also common in babies, denture wearers, PCP, 990 in adults and 1650 in children. Several studies from

individuals using inhaled steroids for asthma, leukemia and different African countries found the incidence of PCP in HIV-

transplant patients and people receiving radiotherapy for head positive patients to vary from 1.25–49% [52].

and neck cancers, but we have been unable to estimate incidence of The relative infrequency of pneumocystosis is due to the low

these cases. prevalence of P. jirovecii in the African environment and lack of

rVVC is defined as four or more episodes of vulvovaginal appropriate diagnostic means, such as bronchoalveolar lavage and

candidiasis per year. This is a surprisingly common health problem trans-bronchial biopsy [53]. PCP may occur in other immunosup-

in sexually active women. rVVC is relatively common in Coˆte pression contexts, including solid organ transplant patients

d’Ivoire with C. albicans as the main causative agent. In Coˆte (kidney in particular), lymphoma or in patients receiving long-

d’Ivoire, a cross-sectional study of 400 women attending an STD term corticosteroids. In these cases the clinical picture is often

clinic found – 40% had evidence of VVC [45]. This same cohort was more brutal and the symptoms more frequently require admission

later re-analysed for rVVC and 23.5% of adult women were to intensive care unit. We were unable to assess the incidence of

apparently affected by rVVC [46]. This is however a select these cases in the absence of any data.

population and so the denomitor will be larger than 400, but it Invasive aspergillosis (IA) was estimated in leukaemia, lung

is not clear how large. Considering the actual adult female malignancies, COPD and HIV/AIDS. It was assumed that 10% of

population size, our estimate of rVVC prevalence is 421,936 cases acute myeloid leukaemia (and an equal number of other leukaemia

of rVVC at a rate of 1675 females per 100,000 person-years, but the and lymphoma patients), 2.6% of lung cancer patients [54] 1.3% of

real figure may be higher than this (and we have used 6% in our COPD hospital admissions (65,500) and 4% of HIV/AIDS deaths

estimate [Table 2]). About one in four women with VVC developed (16,000) [55] develop IA. We estimate an annual incidence of

rVVC, a significantly higher proportion than that reported in the 1550 cases. Very few of these diagnoses are currently established

literature, which ranges from 6 to 9% in European and North in Coˆte d’Ivoire and the optimal therapy of voriconazole is

American women [47,48]. This relatively high rate seems to unavailable. Globally over 300,000 individuals develop IA annually

corroborate previous studies suggesting an association of rVVCs with mortality rates ranging between 30% and 95% despite recent

with the black people [47,49,50], suggesting that genetic factors advanced HIV disease is a significant risk factor for the develop-

related to being black are responsible for the high susceptibility of ment of IA [56,57]. We known that the diagnosis of IA can be

women of this racial group to rVVC [50,51]. However, these challenging: host risk factors, clinical symptoms and radiological

putative genetic factors may not explain alone this relatively high findings must be put into context. Demonstration of morphological

rate of rVVC. Host-related and behavioural factors could also be features consistent with Aspergillus species or recovery of

associated with the occurrence of these recurrences. Aspergillus from a tissue sample is required to define a positive

(definitive) case. Obtaining tissue samples is often problematic in

Fungal related respiratory diseases these multi-morbid patients and the yield of fungi in culture is low,

difficult to interpret and prior antifungal prophylaxis further

Respiratory diseases including TB and asthma are major causes reduces its sensitivity [58,59]. Detection of Aspergillus antigen

of morbidity and hospital admissions in Coˆte d’Ivoire. Exacerba- (galactomannan) by Elisa or more recently immune-chro-

tions of asthma are common and may be driven by fungi, especially matographic technology (lateral flow devices) have been shown

Aspergillus spp, which is common in the environment and colonise to be much more sensitive than culture [60] but which

the airways. ABPA, CPA and SAFS frequencies are thus anticipated unfortunately are not yet available in the country. Just as IA cases

4

D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx

are challenging to diagnose, so is mucormycosis and we have not sub-Saharan Africa, where 70% of HIV/AIDS infections are concen-

estimated this life-threatening infection. trated. Neuromeningeal cryptococcosis (NMC) is the most serious

form of this infection. Death is inevitable in the absence of antifungal

Superficial fungal infections treatment and mortality remains high despite it. The incidence of this

pathology varies from 2 to 30% in HIV-positive patients. However,

Approximatively 25% of the general population have superficial epidemiological data of this pathology for Africa are limited. We

fungal infections of skin and nails, that are caused by dermato- estimated 4590 cases of NMC among adult HIV/AIDS patients, using a

phytes [61]. Children constitute the most affected population, 12.7% rate from a study Osazuwa et al. [19] However, two hospital-

especially in playgrounds, and thus are more likely to be in closer based studies in Coˆte d’Ivoire [68,69] reported a surprisingly low

contact with sources of fungal pathogens. Tinea capitis is very prevalence of rate of 0.6 and 3.6 and they cannot be generalized to the

common in children of sub-Saharan countries particularly in Coˆte population because of selection bias such that many patients with

d’Ivoire. In a large epidemiology study conducted in 2013, 13.9% of cryptococcal infection probably died before either being tested for

17,745 children were found to be positive, mainly with anthro- HIV or attending the clinic and by the lack of use of cryptococcal

pophilic , such as soudanense and antigenemia (CRAG) test which is not yet routinely available in

Microsporum langeroni [28]. We thus estimated that 1,295,786 hospitals. Cryptococcal antigenemia (CRAG) is detectable a median of

school children suffer from tinea capitis according to this 22 days before the onset of symptoms [70] and was shown to be 100%

epidemiological study. A similar pattern and frequency is seen sensitive for predicting the development of NMC in the first year of

in other West Africa countries including Nigeria [62], Guinea [63] ART [71], and is also associated with both NMC and mortality [72]. In

and Senegal [64]. view of these observations, screening for subclinical or asymptomatic

Superficial fungal infections are more rarely caused by non- infection by a serum CRAG assay in patients with advanced HIV

moulds (NDM) attacking the skin or nails. A infection, and giving antifungal therapy to those testing positive, may

longitudinal analysis of clinical data in the last 10 years shown prevent the development of NMC.

the increased prevalence of filamentous fungi involved in

superficial in Coˆte d’Ivoire. We have recently found Histoplasmosis

Aspergillus flavus (24.3%) Penicillium sp (22.9%), sp (17.2%),

and Aspergillus niger (15.7%) from clinical samples primarily of Histoplasmosis is one of the opportunistic infections associated

nails but also intertrigo and mucosal infections (data unpublished). with AIDS. Most diagnoses of histoplasmosis are made post-

This data was confirmed by a recent review of 42 epidemiological mortem, as pre-mortem confirmatory tests are unavailable. The

studies from Bongomin et al. [65], showed that due autopsy study carried out in Coˆte d’Ivoire on 70 HIV-positive

to Aspergillus spp. varies between < 1 and 35% of all cases of patients who died revealed only 1.42% histoplasmosis [73]. Other-

onychomycosis in the general population and higher among wise, histoplasmosis in children or the immunocompetent subject

diabetic populations (accounting for up to 71%) and older people. are very rarely described and the clinical presentation is often

A single case of infection of the face is described misleading. But in Coˆte d’Ivoire two cases of histoplasmosis in

[66]. A small number of mycetoma cases are described [67]. No immunocompetent patients are recorded:

cases of sporotrichosis or chromoblastomycosis are described. var. capsulatum in a patient 36 years and without blemish [74] and

Fungal keratitis is seen clinically but rarely confirmed. Based on a Histoplasma capsulatum var.duboisii in a child [75]. We estimate

global analysis and using data from East Africa, we estimate 3,351 513 acute disseminated cases based on 1.42% of HIV-infected

cases annually. Clearly, this needs confirmation and it is likely that patients. Our estimate could be an underestimate with a 13% rate

all these eyes go blind, or have to be removed. of histoplasmosis among HIV-positive patients with persistent

fever and coughing associated with cutaneous lesions reported by

Cryptococcosis Mandengue et al. in Cameroon [76] and also the fact that we have a

few skilled personnel and facilities to make the diagnosis. In AIDS,

The emergence of Cryptococcus infections has dramatically 10–40% of patients present with skin lesions, which could facilitate

changed the epidemiology of cerebro-meningeal disease in rapid diagnosis if biopsied and examined histopathologically.

Table 3

Antifungal agents available in Coˆte d’Ivoire and whether included in the essential medecines list.

Antifungal agent Available On EML Hospital use Community pharmacy availability

Systemic agents

Amphotericin B Yes Yes Yes Yes

Lipid amphotericin B No – – –

Fluconazole Yes Yes Yes Yes

Itraconazole Yes Yes No Yes

Ketoconazole Yes Yes Yes Yes

Terbinafine Yes Yes Yes Yes

Griseofulvin Yes Yes Yes Yes

Flucytosine No – – –

Voriconazole No – – –

Capsofungin No – – –

Micafungin No – – –

Anidulafungin No – – –

Topical agents

Natamycin eye drops No – – –

Nystatin Yes – Yes Yes

Miconazole Yes Yes Yes Yes

Econazole Yes No Yes Yes

Cyclopiroxolamine No – – –

EML: WHO essential medicine list.

5

D. Koffi, I.V. Bonouman, A.O. Toure et al. Journal of Medical Mycology xxx (xxxx) xxx

Antifungal therapy Patient consent for publication

Despite an increase in antifungal treatments over the past two Not required.

decades, treatment outcomes are still disappointing. Delays in

Funding

diagnosis and fungal identification greatly limit the efficacy of

therapy. Restrictions in route of administration, spectrum of This research did not receive any specific grant from funding agencies in

activity, and bioavailability of some antifungal, especially in HIV/ the public, commercial, or not-for-profit sectors.

AIDS and drug interactions hampers treatment success.

There are some antifungal agents available in Coˆte d’Ivoire

Contribution of authors

that are included in the country’s essential medicines list (Table

3), including fluconazole, itraconazole, amphotericin B

DWD, TOA and DK conceived and designed the protocol. DWD

[77]. Many are off patent with numerous generic formulations.

and DK drafted the manuscript with some adds of TOA. DWD, MD,

Very large numbers of topical azoles are available clinically for

IVB, FK, AM, REMN, KS and DK revised successive drafts of the

thrush and superficial infections; but these are not covered in

manuscript. All authors approved the final version of the

this report. Conventional amphotericin B treatment is largely

manuscript.

used in the hospitalized patient for systemic infection. In

Cameroon and Zimbabwe, about 100,000 days of amphotericin Disclosure of interest

B therapy are estimated annually. But in Mozambique and DRC,

The authors declare that they have no competing interest.

an estimated 200,000 days of amphotericin B therapy are needed.

Flucytosine is not available in Coˆte d’Ivoire although it has been

Acknowledgements

on the WHO EML since 2013. Itraconazole is not available in

Senegal, Gambia, Burundi and Eritrea, and probably some other

The authors thank all authors, clinicians and medical laboratory

countries. The total estimated market for itraconazole capsules

scientists who provided unpublished information from either

in Cote d’Ivoire and other antifungals has not been estimated.

previous works or clinical practice which was necessary in carrying

Natamycin eyedrops is also not available but critically important

out this work. We are also grateful to Ms. Hortance Aman and Mr.

for fungal keratitis.

Armand D. TRE BI respectively from Institut National de la

Because of the increasing of antifungal drug resistance,

Statistique (INS Coˆte d’Ivoire) and Department of Computing and

evidence emphasis on diagnostic testing has several merits. First,

Health Information (Ministry of Health and Hygiene, Coˆte d’Ivoire)

it can establish the correct diagnosis, with both immediate and

for their valuable contribution in National data searching and

longer term implications for therapy – cryptococcal meningitis

retrieval.

being an excellent example. Second, exclusion of a fungal diagnosis

can allow stopping of therapy – a good example is discontinuing

high dose (and often toxic) cotrimoxazole for PCP [78], as well as References

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